An immunological biomarker to predict MTX response in early RA

Ponchel, Frédérique; Goëb, Vincent; Parmar, Rekha; El-Sherbiny, Yasser M.; Boissinot, Marjorie; El-Jawhari, Jehan J.; Burska, Agata; Vital, Edward M; Harrison, Stephanie R; Conaghan, Philip G.; Hensor, Elizabeth M A; Emery, Paul

doi:10.1136/annrheumdis-2013-203566

Cited by 53 publications

(53 citation statements)

References 32 publications

(30 reference statements)

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“…Defining Tregs based on only CD4 + CD25 +/high without the use of CD127 or FOXP3 markers may account for some of the conflicting results [50]. A recent study showed that frequencies of Tregs (defined based on FOXP3 expression) are lower in patients with ueRA than in HCs [51]. On the contrary, we saw an increased frequency (based on FOXP3 expression) or similar frequency (based on CD25 + CD127 low expression) of circulatory Tregs in patients with ueRA compared with that in HCs.…”

Section: Discussionmentioning

confidence: 97%

Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects

Pandya

Lundell

Hallström

et al. 2016

Journal of Leukocyte Biology

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The pathogenic role and frequency of T cell subtypes in early rheumatoid arthritis are still unclear. We therefore performed a comprehensive analysis of the circulating T cell subtype pattern in patients with untreated early rheumatoid arthritis compared to healthy control subjects. Peripheral blood mononuclear cells were obtained from 26 patients with untreated early rheumatoid arthritis and from with 18 age- and sex-matched healthy control subjects. T helper cell types Th0, Th1, Th2, Th17, and Th1/17 and nonclassic T helper subsets were defined by flow cytometry based on the expression of chemokine receptors CCR4, CCR6, and CXCR3. Regulatory T cells were defined by expression of CD25 CD127 and also FOXP3 CXCR5 cells among regulatory and nonregulatory T cells were defined as T follicular regulatory and T follicular helper cells, respectively. The phenotype of T cell subsets was confirmed by transcription factor and cytokine secretion analyses. Multivariate discriminant analysis showed that patients with untreated early rheumatoid arthritis were segregated from healthy control subjects based on the circulating T cell subset profile. Among the discriminator subsets, CCR4CXCR3 (Th2 and Th17), CTLA4 and FOXP3 subsets were present in significantly higher frequencies, whereas CCR4 (Th1/Th17, CCR6CCR4CXCR3, and Th1) subsets were present in lower frequencies in patients with untreated early rheumatoid arthritis compared with healthy control subjects. The proportions of Th2 and Th17 subsets associated positively with each other and negatively with the CXCR3/interferon γ-secreting subsets (Th1 and Th1/Th17) in patients with untreated rheumatoid arthritis. The proportions of Th2 cells increased with age in patients with untreated early rheumatoid arthritis and healthy control subjects. The dominance of circulating CCR4CXCR3 T helper subsets (Th2 and Th17) in untreated early rheumatoid arthritis point toward a pathogenic role of these cells in early stages of the disease.

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Section: Discussionmentioning

confidence: 97%

Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects

Pandya

Lundell

Hallström

et al. 2016

Journal of Leukocyte Biology

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“…What directs this process to the joints is unknown and it probably includes biomechanical factors, neuro-immuno-endocrinological interactions and altered articular microvascular microenvironment. Several factors have been proposed to have an association with the susceptibility and severity of rheumatoid arthritis [1][2][3][4][5][6][7][8][9][10].…”

Section: What Is the Origin Of This Complex Cytokine Response?mentioning

confidence: 99%

“…While we do this, we are generally treat the "normal and abnormal cytokine response" at the same time, because we do not know the main etiology of this abnormal cytokine response. To beter manage RA, we should understand the role of cytokines and the relation between the efector cells [1][2][3][4][5][6].…”

Section: Cytokine and Rheumatoid Arthritismentioning

confidence: 99%

Cytokines in Rheumatoid Arthritis (RA)

Nalbant¹,

Birlik²

2017

New Developments in the Pathogenesis of Rheumatoid Arthritis

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Cytokines are cell molecules that are secreted by immune cells and aid cell to cell communication in immune responses and stimulate the movement of cells towards sites of inlammation, infection and trauma. So, the cytokines are the main part of the immune network to provide the communication in rheumatoid arthritis (RA) too. In RA, cytokines may be classiied into four groups: pro-inlammatory cytokines, inlammatory cytokines in joints, anti-inlammatory cytokines and natural cytokine antagonists. After the initial stimuli have occurred, cytokines play a role in communication between the parts of immune system in every step of the pathophysiology process of RA. The diferentiation of narve T cells into Th17 cells results in inlammation (synovitis) in joints. B cells further the pathogenic process through antigen presentation and autoantibody and cytokine production. The release of cytokines, especially tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1, causes synovial inlammation. In addition to their articular efects, pro-inlammatory cytokines promote the development of systemic efects (anemia, cardiovascular disease, fatigue and depression). So, cytokines are the main molecules contributing to all facets of the disease.

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“…Conflicting non-statistically significant associations between age and response were found (Figure 1a). [1][2][3][4] Female gender was found to be a predictor of non-response in two studies (OR (odds ratio) 0.55 and 0.54), but these findings could not be replicated in two other studies (Figure 1b). [1][2][3][4] In two studies, smoking predicted non-response (adjusted OR 0.35 and 0.60), but this was inconsistent over all response criteria assessed (Figure 1c).…”

mentioning

confidence: 99%

Ab0276 is Prediction of Clinical Response to Methotrexate in Individual Rheumatoid Arthritis Patients Possible? Results of a Systematic Literature Review

Roodenrijs

Goes

Welsing

et al. 2019

Abstracts Accepted for Publication

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ObjectivesTo identify, by a systematic literature review, predictors of clinical response to methotrexate (MTX) treatment in rheumatoid arthritis (RA) patients, which would facilitate personalised treatment.MethodsPubMed and Embase databases were searched for original articles. Additionally, congress abstracts of European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) annual meetings of the past 2 years were screened. Articles describing baseline predictors of clinical response to MTX after 3 to 6 months were included, since this reflects the time span used to determine treatment effectiveness and decide on treatment changes in treat-to-target recommendations.Results30 articles were included, containing 100 different predictors and 11 predictive models, but only 19 predictors and 2 predictive models were studied in multiple similar RA cohorts. Of these 19 predictors, 4 were described in multiple articles sharing details on statistical analyses and response outcomes, allowing pooling of the predictive values of these 4 factors (Figure 1). Conflicting non-statistically significant associations between age and response were found (Figure 1a).1-4 Female gender was found to be a predictor of non-response in two studies (OR (odds ratio) 0.55 and 0.54), but these findings could not be replicated in two other studies (Figure 1b).1-4 In two studies, smoking predicted non-response (adjusted OR 0.35 and 0.60), but this was inconsistent over all response criteria assessed (Figure 1c).3,5 Higher disease activity score was a predictor of response in two studies (adjusted OR 1.12 and 2.7), conflicting and non-statistically significant predictive values were found in two other studies (Figure 1d).2-4,6 Rheumatoid factor positivity predicted non-response in two studies (adjusted hazard ratio 0.61, adjusted OR 0.4), although this was not found in three other studies.2-4,7,8 Heterogeneity between studies prohibited pooling of predictive values. Additionally, a validated epigenetic model was found: area under the receiver operating characteristic curve 0.90 in the development cohort and 0.91 in a validation cohort.9ConclusionNo predictors were identified reliably predicting clinical response to MTX after 3 to 6 months in the individual patient: clinical predictors were weak. However, a promising epigenetic model was found that needs further validation. Future studies on prediction of response to MTX should focus on combining clinical characteristics with genetic and other laboratory biomarkers and on predicting outcome after 3 to 6 months of treatment, to get closer to personalised medicine.References[1] Kavanaugh, et al. Ann Rheum Dis2017;76:822-3.[2] Ponchel, et al. Ann Rheum Dis2014;73:2047-53.[3] Saevarsdottir, et al. Ann Rheum Dis2011;70:469-75.[4] Wessels, et al. Arthritis Rheum2006;54:2830-9.[5] Saevarsdottir, et al. Arthritis Rheum2011;63:26-36.[6] Tan, et al. Int J Rheum Dis2016;19:482-9.[7] Bugatti, et al. Ann Rheum Dis2017;76:790-1.[8] Stühlmuller, et al. Clin Immunol2016;171:50-61.[9] Carini,...

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An immunological biomarker to predict MTX response in early RA

Abstract: Baseline T-cell subset analysis has a value in predicting early RA remission with first therapy with MTX. Immunological analysis could be used in conjunction with clinical/serological features to predict response to MTX and help select the most appropriate therapy at disease presentation.

Cited by 53 publications

References 32 publications

Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects

Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects

Cytokines in Rheumatoid Arthritis (RA)

Ab0276 is Prediction of Clinical Response to Methotrexate in Individual Rheumatoid Arthritis Patients Possible? Results of a Systematic Literature Review

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